You are in hospital lounge waiting to visit a sick friend. A young man sitting next to you explains that his father is very ill. The doctors believe that he has a week to live at most. He explains further that his father has a substantial life insurance policy that expires at midnight.

If his father dies before midnight, this young man will receive a very large sum of money. He says that the money would mean a great deal to him and that no good will come from his father's living a few more days. He offers you half a million dollars to go up to his father's room and smother his father with a pillow.

Is it appropriate for you to kill this man's father in order to get money for yourself and this young man?

In unrelated news, the figure below is from a cool article that presents four alternative hypotheses regarding the effects of tool-use on the visuotactile representation of peripersonal space (Fig 1., Holmes et al. 2004).

The effects of tool-use on the brain’s representation of the body and of the space surrounding the body (‘peripersonal space’) has recently been studied within a number of disciplines in cognitive neuroscience, and is also of great interest to philosophers and behavioural ecologists. To date, most experimental findings suggest that tool-use extends the boundary of peripersonal space – visual stimuli presented at the tips of tools interact more with simultaneous tactile stimuli presented at the hands than visual stimuli presented at the same distance, but not associated with the tools. We studied the proposed extension of peripersonal space by tool-use by measuring the effects of three different tool-use tasks on the integration of visual and tactile stimuli at three distances from participants’ hands along two hand-held tools. When the tool-use task required using the shafts or the tips of the tools, visuotactile interactions were stronger at the tips of the tools than in the middle of the shaft. When the handles of the tools were used, however, visuotactile interactions were strongest near the hands and decreased with distance along the tools. These results suggest that tools do not simply ‘extend’ peripersonal space, but that just the tips of tools actively manipulated in extrapersonal space are incorporated into the brain’s visuotactile representations of the body and of peripersonal space.

Much more common are stories on the psychological toll of war in U.S. military personnel. There's a depressing article in the New York Times Magazine about post-traumatic stress disorder in women soldiers stationed in Iraq.

Many female soldiers have lived through the terrible violence of the war in Iraq. Others have experienced sexual assault — or worse, a combination of the two. They have found themselves struggling to cope with their lives.

Among other examples, the article recounts the ordeal of Suzanne Swift, a 21-year-old Army specialist, who went AWOL rather than return to a second tour of duty in Iraq:

Despite the fact that military procedure for dealing with AWOL soldiers is well established - most are promptly court-martialed and, if convicted, reduced in rank and jailed in a military prison - Suzanne Swift's situation raised a seemingly unusual set of issues. She told Army investigators that the reason she did not report for deployment was that she had been sexually harassed repeatedly by three of her supervisors throughout her military service: beginning in Kuwait; through much of her time in Iraq; and following her return to Fort Lewis. She claimed too to be suffering from post-traumatic stress disorder, or PTSD, a highly debilitating condition brought on by an abnormal amount of stress. According to the most recent edition of The Diagnostic and Statistical Manual of Mental Disorders, used by mental-health professionals to establish diagnostic criteria, PTSD symptoms can include, among other things, depression, insomnia or "feeling constantly threatened." It is common for those afflicted to "re-experience" traumatic moments through intrusive, graphic memories and nightmares.

Given their current track record of providing adequate medical care to returning veterans, will the current administration find the funds to improve the standard of care not only for the physically wounded (see the Walter Reed debacle), but also for the astonishingly large number of vets (33%) diagnosed with mental illnesses?

The V.A. notes that as of last November, [almost] one-third [see Seal et al., 2007] of the veterans of Iraq and Afghanistan treated at its facilities were given diagnoses of a mental-health disorder, with PTSD being the most common. So far, the V.A. has diagnosed possible PTSD in some 34,000 Iraq and Afghanistan veterans; nearly 3,800 of them are women. Given that PTSD sometimes takes years to surface in a veteran, these numbers are almost assuredly going to grow.

What are the appropriate treatments for women with PTSD? Surely not this one:

While serving in a mostly male reserve unit in Kuwait, [another soldier] was sexually assaulted. After returning home to Michigan, she began exhibiting symptoms of PTSD - jumpiness, intrusive thoughts and nightmares - and promptly went to her local V.A. hospital for help. She was then put into group therapy - which has long been shown to be an economical and reasonably effective way of helping trauma survivors process their experiences - but her "group" was made up entirely of male Vietnam vets, some of whom were trying to work through sex crimes they committed during military service. Others came home from war and beat their wives. "I freaked out," the female reservist told me. "It sent me into a complete tailspin."

OBJECTIVE: The authors report an 8-week, double-blind, randomized controlled trial of guanfacine versus placebo for posttraumatic stress disorder (PTSD). METHOD: Veterans with chronic PTSD who were medication-free or receiving stable pharmacotherapy were randomly assigned to guanfacine (N=29) versus placebo (N=34). RESULTS: Guanfacine had no effect on PTSD symptoms, subjective sleep quality, or general mood disturbances. Guanfacine was associated with a number of side effects. CONCLUSIONS: These results do not support the use of alpha 2 agonists in veterans with chronic PTSD.

Guanfacine is an antihypertensive drug and an alpha-2 adrenergic agoninst that binds to autoreceptors on locus coeruleus (Berridge & Waterhouse, 2003) neurons [when administered at high doses1], thereby inhibiting their activity and hence, the release of norepinephrine. When administered at low doses, guanfacine binds to post-synaptic alpha-2 receptors in places like the prefrontal cortex (Arnsten et al., 1988).

Another blood pressure medication, propranolol (a beta blocker), has been more widely used as a potential treatment for anxiety disorders and PTSD (e.g., Strawn & Geracioti, 2007). Similar to the use of alpha-2 agents, the idea behind propranolol is to normalize the hyperactive noradrenegic system in PTSD (a state produced by exposure to extreme levels of stress). Excessive norepinephrine (and the associated signal transduction activity) is thought to result in a trauma-induced enhancement of memory encoding for the harrowing event (Debiec & LeDoux, 2006).

Animal models of fear conditioning have been used to assess possible pharmacological treatments targeting the amygdala, a critical region for fear learning (Debiec & LeDoux, 2006). These treatments aim to impair memory consolidation and reconsolidation (reactivating a memory by retrieving it):

A single, specific memory has been wiped from the brains of rats, leaving other recollections intact.

The study adds to our understanding of how memories are made and altered in the brain, and could help to relieve sufferers of post-traumatic stress disorder (PTSD) of the fearful memories that disrupt their lives.

When reactivated, memories enter a labile, protein synthesis–dependent state, a process referred to as reconsolidation. Here, we show in rats that fear memory retrieval produces a synaptic potentiation in the lateral amygdala that is selective to the reactivated memory, and that disruption of reconsolidation is correlated with a reduction of synaptic potentiation in the lateral amygdala. Thus, both retrieval and reconsolidation alter memories via synaptic plasticity at selectively targeted synapses.

In that experiment (and others like it), rats were treated with the MEK Inhibitor, U0126 [which inhibits the kinase activity of MAP kinase kinase, or MEK -- aka MKK or MAP2K2], not propranolol. U0126 is not exactly approved for human use3.

So what about propranolol for PTSD? According to Strawn & Geracioti (2007),

The utility of these anti-adrenergics in the clinical treatment of PTSD remains to be determined, though it is possible that they may prove to have primary roles in a disorder that is only modestly responsive to antidepressant treatment.

Footnotes

1 Or so the story went, a story that motivated the idea of guanfacine treatment in the first place. However, recent work (Ramos & Arnsten, 2005; Arnsten & Li, 2007) has shown that alpha-2 receptors are much more prominent post-synaptically, and guanfacine is more selective for those than for pre-synaptic autoreceptors (and is selective to a greater extent than clonidine, another alpha-2 blood pressure med known to produce sedation).

3 We're getting way out of my league here, but apparently U0126 is in the very "early clinical phase" for cancer treatment (a "Target for the Future") and is viewed as a "radical approach to stroke therapy." The only published studies have been done with cell cultures, with a few in live rodents.

But this doesn't as a statement make any sense "their antenna-like cell body is able to convey our social emotions across the entire brain". Neurons fire action potentials and the best they can conduct is patterns of firing or epsps/ipsps. They can't convey something as complex as 'social emotions'! That sounds like very sloppy thinking, even if they conduct something, some pattern, some information, to other brain regions its not 'saturating other brain regions with the same feeling'.

Jonah responded to this criticism:

The comment, of course, is true. Neurons traffic in electricity and neurotransmitter. A squirt of dopamine isn't a feeling; it's just a squirt of dopamine.

. . .

And yet, I'm also not planning on abandoning my "reification" of brain cells anytime soon. I still think it's acceptable to refer to spindle cells as conveyors of social emotion, or to allude to dopamine neurons as representing feelings of pleasure. Although no subjective experience - like a feeling - can be literally reduced into a discrete neural circuit, I think such writerly approximations are acceptable. ... It's a necessary inaccuracy, a way of collapsing different levels of scientific description.

He went on to suggest that

a significant and growing body of evidence suggesting that our spindle neurons are involved in the transmission of social emotion and social intuition.

Not to be a snarky cranky critic or anything, but I disagree about the strength of that evidence (and responded thusly)...

Based on the cited comments from Allman et al. (2005), I can see why you might think that spindle neurons transmit social emotions. However, their Trends in Cognitive Sciences article was categorized under the Opinion section with the title, "Intuition and autism: a possible role for Von Economo neurons" [my emphasis]. The article is highly speculative. No neurophysiological studies of spindle cells have ever been conducted, for obvious reasons (no single-unit recording in chimps or humans or humpback whales). So nothing is known about their physiological properties. Nothing is even known about their target projection sites (Allman et al., 2005): "However, it is not known where the VENs ultimately project."

"These findings suggest that, if any social organization does exist, it is formed transiently when needed rather than being a constant feature of the population, and hence is more likely based on reciprocal altruism than kin selection."

...with all due respect to science writers (outside the blog format) who are faced with inadequate space, editors who push to simplify, and deadlines.

Oh, and Patrick Hof, another expert spindle cell neuroanatomist who is not John Allman, is more circumspect about their functional significance.

Hey.. I read this paper, and for what its worth, seems to me the entire bloody brain is sensitive to humor (green in Figure 4), including the (unsexy) temporal cortex. bilateral inferior frontal gyri and more.

But wait, activity that correlates with subjective feeling of funniness (fig 2,3) is also found in white matter (!!) and the ventricles (!) so how much can we trust the rest of the data? (and SPM has the unsettling tendency to project both sulcal and gyral activity to the surface of the cortex in their graphical displays, which is misleading)

So lets put some of this in context: Von Economo cells are part of a larger system (just like mirror neurons are part of larger systems), and possible involved in the integration of information that is needed to 'get' jokes (especially verbal ones). Focusing on them, for whatever reason, in this article is likely to be as an arbitrary political decision akin to those papers that focus on "mirror neuron areas" when its clear the entire brain is involved in imitation.

Anyway, we are a homogenous group, all more or less identical, and we meet every Thursday night in a secret fairy dell that lies within a beautiful ferny glade in the old-growth forest - the moral high ground you might say, where we practise preaching and the double standards for which we are famous. We hug trees and skip about celebrating atheism and moral cancer, and indulge in the sublime pleasure of gleefully ignoring the human rights abuses of terrorists and certain fascist regimes. We achieve this state of rapture and denial by drinking chardonnay and losing ourselves in reminiscences about the '60s when we were all promiscuous hippies living on social welfare, smoking dried banana peel and making snide jokes about Vietnam War veterans.

Let me tell you, it's such fun. We sway about under the moonlight in our dirty old fantasies and tattered kaftans to the sound of the Rolling Stones - it's a hideous, repugnant and deeply disturbing spectacle, and I love it.

BUDAPEST, HUNGARY, March 9 – Ever wonder why some women seem to be more ill-tempered than others? University of Pittsburgh researchers have found that behaviors such as anger, hostility and aggression may be genetic, rooted in variations in a serotonin receptor gene. Indrani Halder, Ph.D., of the Cardiovascular Behavioral Medicine Program at the University of Pittsburgh, will present the findings today at the American Psychosomatic Society's Annual Meeting, held in Budapest, Hungary.

Previous studies have associated the hormone serotonin with anger and aggression in both humans and animals and have shown that increased serotonin activity is related to a decrease in angry and aggressive behaviors. In the study being presented today, researchers sought to determine if this relationship was genetically determined. The study is the first to look at the relationship between variations in the serotonin receptor 2C gene and anger and hostility.

But seriously, I feel sorry for Britney. The Neurocritic has never been a fan, but the amount of Schadenfreude heaped upon the poor girl is excessive. Whether she has a substance abuse problem or the onset of a serious mental illness, the public and the press should be a little more compassionate...

Plus, are anger and hostility (whether in women or in men) really so simple? Professor Robert Plomin, deputy director of the Social, Genetic and Development Psychiatry Centre, London, is skeptical:

"Because the Halder paper looks at only one gene in a relatively small sample, I bet that this report will join the ranks of thousands of other reports that fail to replicate. On the other hand, in dozens of studies of humans and rodents, serotonin has been shown to play a role in emotional responding so it is not unreasonable to consider DNA variations in the serotonin transporter as a source of individual differences in aggression and anger. I would just need a lot more convincing."

To slow the progress of Parkinson’s disease, doctors planted electrodes deep in my brain. Then they turned on the juice.

By Steven Gulie

I'm lying in an operating room at the Stanford University hospital, head shaved, waiting for my brain surgery to begin. Sure, I feel anxious, but mostly I feel crowded. There are 10 people milling about, tinkering with instruments and examining me. It’s an impressive crew, including a neurosurgeon and his fellow, a neurologist and her fellow, an anesthesiologist, an experimental physicist, and a graduate student in electrical engineering. That’s right, a physicist and an electrical engineer. Directly behind me, out of my sight, is the star of the show, chief neurosurgeon Jaimie Henderson: 44 years old, tall, erudite, and handsome. On my right, flexing my hands, is neurologist Helen Bronte-Stewart: brisk, smart, and beautiful. In fact, nearly everyone is not only brilliant but also pretty enough to play themselves in the movie version of this story. I call them Team Hubris.

The procedure has been remarkably successful, allowing most patients to resume their normal activities after being held captive by tremors, rigidity, and bradykinesia for years:

Today, eight years since the first signs of Parkinson’s and after months of fiddling, my body is almost free of symptoms. With the stimulator turned off, a Parkinson’s test shows 20 significant impairments. With the stimulator on, it drops to two. Add just a touch of L-dopa and it drops to zero.

The last wisps of fog have cleared away. My jokes make people laugh again. I can keep up with conversation. I can ride a bike. I can write. It’s been five months since the surgery, but it has finally all come together: It works. I forget that I even have Parkinson’s most of the time. And last November, I went back to work full-time. It’s a miracle. A second chance at life.

To my knowledge, there have been no protests about conducting invasive brain surgery on people with neurological disorders such as Parkinson's, primary generalised dystonia, atypical tremor syndromes, and epilepsy. However, when the same general procedure (with different neural targets, of course) is used for a psychiatric disorder, rabid virulent critics crawl out of the woodwork to call the procedure "butchery" and those who discuss it "disgusting misguided butchers" (among other unmentionable names).

The cause of Tourette syndrome has been controversial ever since Georges Gilles de la Tourette, a neurologist who shared a mentor with Sigmund Freud at the Salpêtrière Hospital in Paris, first described the condition in 1885. Is the syndrome the result of hysteria (Tourette’s hypothesis), repressed sexual conflicts, or oppressive mothers, which were the favored explanations for much of the 20th century? Or is it an organic defect of the brain, as many neuroscientists and physicians now hold? The ability of neuroleptic drugs, beginning with haloperidol in the 1960s, to reduce tics supported the neurologic position.

Or maybe it's just because DBS for TS hasn't gotten the publicity that DBS for depression has received...

An ever-controversial topic in the field of high-level vision and object recognition is the question of whether faces have a privileged status relative to other objects, processed by a special modular region of ventral temporal cortex called the fusiform face area (Kanwisher et al., 1997; Kanwisher & Yove, 2006; McKone et al., 2007), or whether faces are just one example of a stimulus class that requires substantial expertise in order to distinguish between similar exemplars (Gauthier et al., 1999, 2000; Gauthier & Bukach, 2007). A new article in Nature Neuroscience tackles this issue and comes up with a surprising answer.

Thierry and colleagues (2007) recorded event-related potentials (ERPs), which are synchronized brain waves time-locked to the occurrence of particular stimuli or events. In particular, the N170 component is thought to be a highly specific ERP response to faces (as opposed to other objects) that shows a peak at 170 msec after stimulus presentation. This ERP was first reported by Bentin et al. (1996), although other researchers observed a related face-specific response back in the late 80's (Jeffreys, 1989). The N170 is most pronounced at the posterior temporal electrodes and is greater over the right hemisphere than the left.Bentin et al. (1996)

In the new NN paper, Thierry et al. argue that previous studies of the N170 component did not adequately control for variability across stimulus classes, i.e., face stimuli have been much more similar to each other than the non-face stimuli.

From Fig 4a (Thierry et al. 2007)It turned out that interstimulus perceptual variability alone affected the size of the N170, with low ISPV stimuli (both faces and cars) producing a larger N170 than high ISPV stimuli.

Furthermore, when controlling for ISPV, the face-specific effect for the N170 went away. The face N170 peaked earlier in time than the car N170, but they did not differ in amplitude. However, a face-dominant effect for an earlier component, the P1, emerged (which was an unexpected finding, since it suggests that category-specificity can manifest itself at 100 msec, 70 msec before the N170 component).

Hmm, interesting. Why did this happen? The authors are cautious in their interpretation:

On the other hand, the P1, a peak generally regarded as an index of lower level perceptual processing, was surprisingly unaffected by differences in ISPV, but was sensitive to object category in both Experiments 1 and 2. This should not be interpreted as evidence for absolute category selectivity because only three object categories were tested here. Indeed, faces, cars and butterflies differ in terms of overall composition and various perceptual properties such as outline, contrast, subparts and complexity, which were not manipulated here. It is therefore possible that the P1 still reflects perceptual differences between these objects; that is, that apparent category selectivity in this component is an emergent property arising from low perceptual invariants.

Establishing when and how the human brain differentiates between object categories is key to understanding visual cognition. Event-related potential (ERP) investigations have led to the consensus that faces selectively elicit a negative wave peaking 170 ms after presentation, the 'N170'. In such experiments, however, faces are nearly always presented from a full front view, whereas other stimuli are more perceptually variable, leading to uncontrolled interstimulus perceptual variance (ISPV). Here, we compared ERPs elicited by faces, cars and butterflies while—for the first time—controlling ISPV (low or high). Surprisingly, the N170 was sensitive, not to object category, but to ISPV. In addition, we found category effects independent of ISPV 70 ms earlier than has been generally reported. These results demonstrate early ERP category effects in the visual domain, call into question the face selectivity of the N170 and establish ISPV as a critical factor to control in experiments relying on multitrial averaging.

Once again the chicken/egg argument is revisited vis-a-vis addiction. Do drugs make us impulsive or does impulsivity make us do drugs?

A new article in Science shows evidence that a paucity of functional D2/3 receptors in the ventral striatum "high-impulsivity" rats is correlated to a higher tendency to self-administer cocaine when given access to drug.

The implications are positive, in that it is always good to see work that supports a non-moral-depravity line of reasoning behind addiction; on the other hand, some reports in the more mainstream news take a harder nature/nurture line with headers like "Study: Addicts born, not made." and that sort of thing. I always worry about backlash from social scientists whenever I see stuff like that.

About Me

Born in West Virginia in 1980, The Neurocritic embarked upon a roadtrip across America at the age of thirteen with his mother. She abandoned him when they reached San Francisco and The Neurocritic descended into a spiral of drug abuse and prostitution. At fifteen, The Neurocritic's psychiatrist encouraged him to start writing as a form of therapy.